First Eat Right - Dietitian Nutritionist Dr. Nafeesa's Diet & Nutrition Clinic

C-section delivery, a rarity in older days has become very common now. Call it a delivery of convenience to overpower nature by bringing in the newborn into this world at an auspicious time fixed by us or as a result of lifestyle changes that hamper the natural delivery mode that leads to failure in labour pain, correct positioning/fixation of the baby’s head and so on. Whatever it is, caesarean rates have spiked up from 6.7% in 1990 to 19.1% in 2014. Various reasons quoted for such increase in rates include advanced maternal age at childbirth, physician fear of litigation, decrease in vaginal births after C-section and access to private health insurance.
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Gut microbiota shapes an individual’s health and babies born through C-section delivery are not exposed to the mom’s vagina as compared to babies born through natural delivery-initial microbiota of the fetus depends on the bacteria composition transferred from the mom to the child via her birth canal. Gut microbiome of c-section babies is not diverse and we have studies showing that their gut microbiome might harvest more dietary nutrients predisposing them to be obese/overweight. There have been numerous theories suggesting that kids born through C-section deliveries face higher risk of being obese/overweight compared to kids born through natural birth. Lets look at various studies that tried to find out the real link between mode of delivery and risk of overweight/obesity.

Evidence from Cohort Study
Detailed here is the growing up in Ireland (GUI) study that recruited 11,134 infants born in Ireland born between Dec 2007 and June 2008. When the infants were 9-months old all the families participated in a face-to-face questionnaire session conducted by trained interviewers. When the child was 3- and 5-years old all the mother-infant pairs followed up with home-based interview sessions. But after imposing various exclusion criteria the research team was left with 11,049 infant-mother pairs at baseline. Even those infants born through vaginal breech delivery were excluded from the study.

Delivery mode was split into four categories namely vaginal delivery (VD), assisted VD, elective/planned caesarean section (CS) and emergency/unplanned CS. Moms who opted for the last two options were either in pre-labour or in labour respectively. The time of labour contractions is important as the offspring’s microbial colonisation begins later. For instance, children born by pre-labour CS have no exposure to vaginal microflora whereas kids born through CS in labour comparatively have an advantageous edge as they are likelier to be exposed to the mom’s microbiome. Each of the child’s height, weight and BMI measurements were taken and they were all classified as thin, normal & overweight/obese depending on the values procured. Breastfeeding practice was also considered as mothers who opted for elective CS were unlikelier to breastfeed and its known that babies who don’t breastfeed are at a higher risk of obesity.

Results
8,175 of the 11,049 infants were delivered vaginally-almost 60% was by normal VD and the rest was by assisted VD. 26% of the deliveries were by CS-12.7% by elective CS and 13.3% by emergency CS. 51.1% of the participants were boys and almost 55% of deliveries were by assisted VD and emergency CS. Among women who opted for elective CS almost 50.4% of them 35 years and above. After birth it was observed that 13.9% kids were macrosomic (more than 4 kilograms), 10.9% were large for gestational age; at the age of 3, 1,767 (18.7%) of them were overweight and 506 (5.3%) were obese and at the age of five, 1389 (15.8%) of them were overweight and 437 (5%) were obese. While 5030 (57%) children were within normal BMI ranges between 3 and 5 years of age 175 (2%) were obese. Almost 3% kids who were obese at age 3 became non-obese at age five while 3% who were not obese at age 3 became obese at age 5. 13.2% mothers who delivered vaginally and 21.5% who delivered by CS were obese.

At 3 years: Results showed that a clear link between elective CS and obesity risk could be found at age 3 compared to those kids delivered vaginally (normal).  Overweight risk was linked to emergency CS and not elective CS. Elective CS was not linked to obesity risk at age 3 among appropriate for gestational age (AGA) infants. Small for gestational age (SGA) infants had a median birth weight of 3 kilogram and there was a link between emergency CS and obesity in AGA non-macrosomic kids.

At 5 years: There was a slight link between elective CS and obesity risk when the children were five years old and a similar link was seen between emergency CS and obesity risk as well.

Between age 3 and 5: Here, no association was found between elective CS and any BMI category transition. Kids born through emergency CS were at an increased risk of remaining obese between 3 and 5 years of age while those born through emergency CS were at an increased risk of making any other BMI transition.
This study doesn’t clearly prove that there is a causal relationship between elective CS and childhood obesity. An increased risk of obesity in kids born through emergency CS and not elective suggests that there is no causal effect due to vaginal microflora.

Obesity Risk in Preschool Kids in China
C-section delivery in some Chinese cities exceed 50% and generally too, rates of birth by CS has increased from 18% in 1992 to 40% in 2000. At the same time, overweight/obesity rates of kids also have increased from 12.6% in 1997 to 22.1% in 2009. A group of researchers set forth to analyse the effect of CS delivery and risk of childhood obesity in a large sample of preschool kids. 9103 kids aged 3-6 years from 35 different playschools in 5 different kids were included whose parents were given a questionnaire. It was observed that 8900 of 9103 were valid and hence, weight and height information of all these children were collected. WHO guidelines were taken for branding a kid to be overweight (BMI between 85th and 95th percentile) or obese (BMI ≥95th percentile). Delivery mode was also noted down classifying the child into one of the following categories-vaginal delivery and CS (elective/non-elective).

Information on the mother’s age, education, smoking and drinking status, pre-pregnancy weight, maternal weight, breastfeeding status and the child’s birthweight and sex were noted. Maternal pre-pregnancy BMI was calculated based on maternal height and pre-pregnancy weight and paternal BMI was also calculated based on weight and height values.

Results
67.3% kids were born via C-section delivery. It was moms who delivered after the age of 36, who were obese/overweight before pregnancy and with a higher education level (who gained more weight during pregnancy) who were at a higher risk of CS delivery. Of the total kids, 939 kids who were delivered through CS were obese and around 25% kids were not breastfed. Of the 5992 CS deliveries, 4016 (67%) were bon-elective and 1977 (33%) were elective. Of notable interest is the fact that paternal age, BMI and smoking status affected the delivery mode. CS delivery increased the risk of overweight/obesity in kids, both elective and non-elective types.

Longitudinal Cohort Study: Ireland
A longitudinal birth cohort with phenotyping of mom and infant was used to probe into the exact association between CS delivery, prelabour CS and childhood body composition and growth. Data for the study was fetched from the Screening for Pregnancy Endpoints (SCOPE) study and its follow-up prospective Irish birth cohort, the babies after SCOPE (BASELINE) study.

Participants from the BASELINE study were recruited around their 15th week of pregnancy in which 1774 gave their written informed consent and 1537 of them had infants recruited into the BASELINE study. The researchers segregated mode of delivery into four different categories namely unassisted vaginal delivery (VD), operative VD, prelabour lowest segment (LS) CS and LSCS in labour. Operative VD included the use of either forceps or vacuum for delivery. Whole body density, height and weight measurements for each infant were calculated and the kid was classified as either thin, normal, overweight or obese depending on BMI values.

Result
Of the 1305 infants 943 of them were delivered vaginally while the rest were delivered by CS: prelabour LSCS (12%) and LSCS in labour (15.8%). 13% of infants were macrosomic at birth and 11% were large for gestational age. At 2 years of age, 116 (10.9%) kids were overweight/obese and at the age of 5, the number increased to 118. Around 6 months the mean BMI of infants delivered vaginally and by CS was 17.3 and 17.6.
When infants were 2 months old there was no link between prelabour CS and body fat percentage (BF%) and LSCS in labour when compared to kids delivered through unassisted VD. Infants delivered through CS had higher BMI at six months of age compared to those born vaginally. But there was no link between prelabour CS or LSCS in labour and risk of being overweight/obese at age 2. When the kid was 5 years old, there was a nonsignificant link between prelabour CS and the risk of being overweight/obese. There is no clear evidence to support the link between prelabour CS and offspring being overweight/obese in early childhood.

No Link between Mode of Delivery & Overweight Risk
A research team was interested in the long-term effect of CS delivery on offspring health as CS delivery rates are presently higher than ever. They compared the BMI of almost 1,00,000 male individuals who were 18 years and divided them into three categories based on their mode of delivery-vaginally, elective C-section or non-elective C-section. Results showed that 5.5% and 5.6% of participants delivered through elective and non-elective C-section were obese compared to 4.9% of men delivered vaginally. The researchers commented that the mom’s weight before pregnancy had a greater impact on inheriting obesity or affecting foetal health in comparison to which mode of delivery played a negligible role in determining obesity/overweight risk. Researchers could observe that mode of delivery did not play a strong role in impacting obesity risk of offspring even after accounting for various factors such as BMI, maternal age, gestational age and presence of diabetes, BP and smoking in the mothers.
Mothers should be more concerned about their pre-pregnancy weight and health, take good care of themselves during the pregnancy tenure and focus on delivering a healthy baby rather than worrying about the mode of delivery.

References
The Impact of Caesarean Section on the Risk of Childhood Overweight & Obesity: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6181954/pdf/41598_2018_Article_33482.pdf

Caesarean Section May Increase the Risk of Both Overweight & Obesity in Preschool Children: https://bmcpregnancychildbirth.biomedcentral.com/articles/10.1186/s12884-016-1131-5

Association between Caeserean Section Delivery and Obesity in Childhood: https://bmjopen.bmj.com/content/9/3/e025051

Study Debunks Notion that C-section Would Increase Risk of Obesity in the Child: https://www.sciencedaily.com/releases/2019/12/191206152948.htm

Different diets have been implemented for the purpose of weight loss and most of them pass the test of time only as fad diets that don’t last long. But there are some others which have been strongly suggested even by physicians and health experts to resolve various health issues in individuals-such as the DASH or Ketogenic diet. The DASH diet has been approved for lowering hypertension and the Ketogenic diet exists as an effective treatment against epilepsy. Almost 70% of people with epilepsy could have their seizures controlled with anti-epileptic drugs (AEDs) and for those whose seizures are not arrested with AEDs, the Ketogenic diet proves to be an effective treatment plan. Following the diet helps in reducing the number of seizures, severity of each and also evoke other benefits.
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The Ketogenic diet (KD) is a high fat, low carbohydrate, controlled protein diet used since the 1920s as an effective treatment for intractable epilepsy. Though its only a modified nutrient intake plan, physicians suggest taking up KD only after two suitable medications have been tried and have not provided any fruitful results. KD might be used for adults and children with maximum monitoring done on infants who have been suggested for the diet. It works on the principle that our body uses glucose from carbs as a source of energy. Chemicals called ketones are formed when our body uses fat as an energy source and a fatty acid called decanoic acid might be involved in the way the diet works. The KD mimics the body’s response to starvation by using fat as the primary energy source in the absence of sufficient carbohydrate source. Though the exact process by which ketosis control seizures is unknown researchers hypothesize that ketones have an anticonvulsant effect when crossing the blood brain barrier. It’s a known fact that the various options available for treating kids with pharmacoresistant epilepsy is limited and even surgery is not a viable option for most of them. Almost 30% kids with seizures remain unresponsive to pharmacologic treatment or suffer from extreme side effects of AEDs. It was then that the International Ketogenic Diet Study Group consisting of 26 paediatric epilepsy specialists and dietitians came to a conclusion that KD should be the suggested mode of treatment for those children who failed 2 or 3 anticonvulsant therapies, especially in those with symptomatic generalized epilepsies.

A meta-analysis of 19 observational studies in 2006 showed that six months after starting a ketogenic diet almost 60% kids were relieved from seizures by more than 50% and 30% kids had almost 90% reduction in seizures. It was kids aged 1-10 with generalized seizures who were maximum benefitted by the diet. Another study conducted sometime later on 145 kids aged 2-16 years suffering from daily seizures randomly divided into the diet or control group showed that seizure percentage was lower in the diet group compared to the control group; 28 kids in the diet group experienced 50% decrease in seizures compared to only 4 in the control group who benefited and 5 kids in diet group had 90% reduction in seizures while none in the control group benefited in such ways.

Single-Centre Retrospective Analysis
KD is a valuable option for those with drug-resistant epilepsy (DRE) which can be given for a minimum period of 3 months and continued for several years if it proves to be beneficial. But, constant monitoring of the child is required to keep it effective and prevent the onset of any adverse short-term or long-term effects which might include any effect on the child’s growth. There isn’t much data regarding the effects of KD on the affected kid’s growth-A study by Peterson et al. showed that participants with marked ketosis were characterized by decrease in height for age z-scores which was not evident in those with low or moderate ketosis. The same was also shown by Spulber et al. in a study of 22 kids showing negative link between child growth rate and blood beta-hydroxybutyrate (β-OHB) concentration. A retrospective study by Nation et al. showed that a caloric and protein intake <80% of the recommended values and protein/energy ratio ≤1.4g protein/100 kcal was linked to decreased growth percentile.

The study here probed into growth changes in 34 kids suffering from DRE (n=14) or glucose transporter type 1 deficiency syndrome (GLUT1-DS, n=20) all of whom were treated with KD for 12 months. Inclusion criteria was that kids should be 2-17 years of age, there should be a diagnosis for DRE or GLUT1-DS and treatment with KD done for at least 12 months. Kids with severe organ failure, thyroid disorders or needing enteral or parenteral nutrition were excluded from the study. Growth, clinical and body composition of the participants were calculated at baseline and 12 months after follow-up. Weekly food diaries were assessed to understand the weekly food caloric intake, food preferences and intolerances and total energy intake was formulated based on every patient’s need. Kids aged 3 months-10 years were assessed of their energy needs every quarter while adolescents were analysed every 6 months. The research group ensured that every participant was provided 0.8-1.0 gram of protein per kilogram of body weight from animal sources such as meat, fish, poultry, eggs and milk. All participants took multivitamin and mineral supplements as per their age and sex.

What started as a 1:1 ketogenic diet went to 2:1, 3:1 or 4:1 ratios and participants were assessed for fasting blood ketones, supplements use and for presence of any adverse effects. Each of the participant’s height, weight, BMI and other measurements were taken.

Results
Median age of study participants was 7.5 years, kids with GLUT1-DS were diagnosed at an older age than those with DRE and hence, started with dietary treatment immediately after diagnosis. All participants with GLUT1-DS were on ambulation and did not take AEDs and 10 patients with DRE were on multiple anti-epileptic drugs of which 5 were not able to ambulate. At baseline, there was no difference in height or other parameters between both set of patients. Even after 12 months of study the median height scores did not change significantly from baseline. The kids were put into three growth pattern groups after 12 months of KD-increased (Group-I), tracking (Group-T) and decreased (Group-D) linear growth. There were 6 kids in Group-I of whom 3 had GLUT1-DS; Group-T had 21 patients of whom 13 had GLUT1-DS and Group-D had 7 kids of whom 4 had GLUT1-DS. The three groups did not differ in characteristics at baseline. There was different in energy intake in Group-T compared to Group-I. 11 of 34 kids refused food intake or incomplete meal consumption at intervals. Not much difference in fasting β-OHB levels after 12 months were observed between the three groups. There was an inverse association between fasting β-OHB blood levels at 12 months and height.

While there was no significant difference in height, weight or BMI scores between the three groups at baseline after 12 months it was observed that height and growth velocity scores were lower in Group-D than in Group-I, weight scores were impaired in Group-D and T than in Group-I. There was no difference seen in fat mass percentage between the groups at baseline nor after 12 months.

A 10-Year, Single-Centre Study on Ketogenic Diet
The KD has been used at the Children’s Memorial Hospital, Chicago since the year 1963 and researchers focused on the effect of the diet in patients under the age of 3 in a span of ten year (April 2004 to June 2014). All the patients were grouped into two-early withdrawal or adherent group. The reason behind early withdrawal was questioned and this involved three clinical features-very short-term efficiency of KD, adverse events and implementation and practise of KD. Those kids who underwent 3 months of KD treatment were further classified into 4 groups based on percentage of seizure reduction 3 months-complete seizure control, >90% improvement, 50-90% improvement and <50% improvement. Anyone who experienced >50% seizure control was categorized as responders and others as non-responders. Patients were also classified based on their age into three groups-<1-year-old, 1-2-year olds and >2 years old. Each of the participants’ calorie and protein needs were calculated and vitamin and mineral supplementation was provided based on food intake and nutrient requirements.

Results
109 patients aged below 3 were given the Ketogenic diet and included in the analysis. The median age at which seizures started in them was around 4 months of age and each of them had used medications at least 4 times before starting the diet. More than 50% of them had West syndrome and all of the 109 participants’ EEG was abnormal at the start of the diet. The youngest patient was 3 weeks old. KD was initiated at a 1:1 ratio (fat grams: carbs + protein grams) increasing up to 3:1 on day 3. 20 patients were on a 3:1 ratio, 13 were on a 3.5:1 ratio and 59 were on 4:1 ration. 4.75:1 was the maximum observed ratio and every child reached a fat: no fat ratio of 3:1 or higher except one kid (2.75:1). Solids (33%), liquids (32%) and a combination of both (33%) were given to the kids. 8 of the kids fed on expressed breast milk, median duration of the diet was 1.1 years and one patient suffered from positive urine ketosis at some point of the diet. There was no response in seizures for 3 months of KD administration.
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But after 3 months, 39% patients (n=42) experienced more than 50% reduction in seizures. Of the 42, 20 (18%) of them accomplished complete seizure control and another 3(3%) experienced >90% seizure reduction. Age was not a matter in enabling seizure reduction in kids following KD. But what surprised the researchers was the fact that a genetic mutation or a chromosomal abnormality in patients improved their response to seizures after starting on the KD diet. Though no adverse effects were seen but constipation was commonly reported in the adherent group who were on the diet for a longer period of time.

This shows that the KD is an effective and safe intervention for kids suffering from epilepsy. But given the advantages, the KD is not suitable for all kids and neither can be called ‘user friendly’ given the time and energy needed to maintain ketosis. Some kids refuse to follow the diet and even parents are stressed when diet-induced social modifications become essential. While many studies report the benefits of the diet the medical consequences of KD are not well documented. For instance, a study by Balaban-Gil et al. showed a 10% rate of serious complications in 52 kids with refractory epilepsy and we even have anecdotal reports of coma and death often blamed on metabolic diseases. Another study by Kang et al. showed that while kids following the diet reaped benefits in seizure control they also started experiencing dehydration and gastrointestinal complications within 4 weeks of diet onset. There were also cases of hypoglycaemia, aspiration pneumonia, serum lipid abnormalities, infectious diseases, electrolyte imbalance and acidosis, hepatitis and acute pancreatitis. Three patients died within 60 days of starting to follow the diet-all of them due to brain damage. But it was also observed that the dropout rate of study participants in the research conducted by Kang et al. was more than the dropout rate observed at other centres. But researchers feel that most complications of KD are temporary and could be managed with effective treatment. Ketogenic diet is complicated maybe even life threatening but with high levels of expertise, experience and monitoring it is possible to make the best of it as much as possible. The diet should be administered only by an expert dietitian who has potential knowledge and expertise in KD.

References
Impact of the Ketogenic Diet on Linear Growth in Children: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6683244/pdf/nutrients-11-01442.pdf

The Ketogenic Diet in Children 3 Years of Age or Younger: https://www.nature.com/articles/s41598-019-45147-6

The Use of Ketogenic Diet in Paediatric Patients with Epilepsy : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3434405/pdf/ISRN.PEDIATRICS2012-263139.pdf
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Food for Thought: The Ketogenic Diet & Adverse Effects in Children: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1198735/pdf/epc_00044.pdf

Exercise might be an integral part of daily routine, a sort of punishment as believed by kids, adolescents and few younger adults too and for few others exercise is their lifeline. While normally a person spends anywhere between 15 minutes and 75 minutes a day exercising there are some who invest 3,4 or 5 hours a day for exercising-it might be their profession, passion or a means to some other end. Too much of anything is not desirable and when individuals start performing too much exercise on any given day, they start feeling extremely tired and even fatigued. High intensity repetitive eccentric exercise causes muscle damage which decreases muscle strength and increases delayed onset muscle soreness (DOMS) and serum creatine kinase (CK) levels.
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Starting a new exercise schedule is interesting and demanding as it involves planning, performing and balancing the newly formed routine. But beyond all these comes the muscle soreness that demands maximum attention-you might be finding it hard to even get out of bed or raise your hands to brush the teeth. Such soreness is something experienced by most individuals when they start working -called as DOMS. DOMS occurs when exercise causes stress to muscle tissue beyond what its accustomed to. Small microscopic tears occur in the muscle and there is damage to muscle fibre. There is damage to cell membrane and an inflammatory response often caused due to eccentric exercise performance such as running downhill, stepping, weight lift, etc. DOMS peaks 24-48 hours after activity and disappears without a trace 5-7 days after exercise. We know that DOMS is inevitable but there have been different research studies that have tried to control its impact with the help of warm-up exercises, stretches, ultrasound therapy, ice therapy, massage and supplementations but unfortunately, they have not been able to come to a definite conclusion regarding any of them. One must note that DOMS doesn’t spare anyone and even bodybuilders and athletes are bound to experience it.

Exercise needs energy to perform, a lot of energy! This leads to the production of free radicals, lipid hydroperoxides, oxidative stress and changes in blood antioxidant concentration. Such markers of oxidative stress lead to oxidative damage and inflammation paving way for the occurrence of metabolic diseases; they also bring about enhanced exhaustion as well as decreased efficiency. Researchers believe that oxidative stress might also be the reasons for DOMS. Hence, the fitness-conscious individuals have always been interested in minimizing oxidative stress via different methods-such as use of supplements rich in micronutrients such as vitamin A, E and minerals. There is the practise of taking these supplements by athletes and other individuals too but their actual effect on stress, insulin metabolism, lipid profiles, muscle recovery and performance remains unknown. Mankind is interested in trying out different ways and means to achieve a goal and that’s known already. We have different medicinal streams including Allopathy, Homeopathy, Ayurveda and so on-each of them are beneficial in their own way although we don’t have evident proofs supporting their effects on mankind. There has been an increased interest in using alternative medicine for treating diseases such as autism spectrum disorder and now, researchers have shown an inclination to use herbal medications such as grape seed extract (GSE) for decreasing oxidative stress in athletes.

Grape Seed Extract
GSE is one of the important supplements used as an anti-inflammatory agent in traditional medicine. Its also a vital source of oligomeric proanthocyanidine (OPC) that’s an excellent antioxidant compound that is touted to provide protection against free radicals. Its believed that GSE provides almost 50 times higher oxidant-lowering effect compared to vitamin C and E and is also a potent source of flavonoids, linoleic acid fatty acids and phenolic procyanidins. Its been already shown that OPC decreased oxidative and lipid damage to the brain, liver and gastrointestinal mucosa in diabetic animals. Another study by Shawo et al. showed that GSE reduced oxidative stress due to H2O2 while certain other studies have proved that GSE is rich in analgesic and anti-inflammatory properties that’s effective in reducing pain and inflammation due to DOMS.

GSE Effect on Preventing DOMS
A double-blind randomized study with 20 young healthy female students with no history of muscular bruising or regular activity for almost 6 months before the trial was conducted. Inclusion criteria included being in a specific period of menstruation, no steroid and non-steroid anti-inflammatory drugs and antioxidant supplements. All the participants were randomly assigned into one of the two groups-GSE (n=10) and control (n=10) group. Members of the GSE group received GSE as a capsule of 400 mg consuming 1200 mg/day, 7 days prior to exercise for 48 hours while members of the control group received lactose in the same fashion. All of them refrained from consuming any other supplements during this period and after the GSE/placebo supplement, an exercise protocol was followed by each participant-warm up for 15 minutes after which they sat in a chair for help with an assistant. CK and LDH (lactate dehydrogenase) levels were measured by taking their sample blood tests.
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Results showed that there was no significant difference between the two groups at baseline in CK, LDH and VAS (visual analogue scale used to measure pain intensity). CK increased in both groups 24 and 48 hours after exercise with no significant difference between groups at any time. There was an increase in VAS scores in both groups after exercise compared to before exercise. VAS scores were significantly lower in the GSE group compared to the PLC group, 24h and 48h after exercise. It was observed that though GSE did not decrease CK and LDH enzyme activity its anti-inflammatory properties are helpful in reducing pain after DOMS.

GSE Effect on Muscle Damage After Eccentric Exercise
The study included 16 healthy male students who did not exercise for the past six months, had no musculoskeletal disease, did not smoke and did not take any supplements. Each of them was randomly assigned to either the GSE (n=8) or control (n=18) group. Each of them performed 2 sets of eccentric exercise consisting of 25 repetitions each with a rest time of 5 min between sets.

Participants in the intervention group consumed GSE extract in capsule form (300 mg) with water once per day in the evening up to 72 hours after eccentric exercise. The placebo consumed capsules containing starch in the same manner. Each of the participant’s maximum muscle strength was measured and the visual analogue scale (VAS) was used to measure muscle soreness. Blood samples were taken to measure CK levels. Results showed that there was no significant interaction between GSE supplementation and maximum muscle strength and muscle soreness. But CK levels showed a significant decrease between GSE and placebo groups, there was a significant decrease in CK levels 96h after exercise in the GSE group compared to the placebo group. This study showed that acute supplementation with GSE after exercise did not affect maximal muscle strength and muscle soreness in the present study.

GSE Supplementation & Effects on the Biomarkers of Oxidative Stress in Female Volleyball Players
This was a randomized, double-blind placebo-controlled trial which included 40 female volleyball players aged 14-42 years after imposing several exclusion and inclusion criteria. All of them were split into two groups-group 1 received 300 mg of GSE (n=20) and group 2 received placebo pearls (n=20) twice a day for eight weeks alongside lunch and dinner. Weight, height and BMI measurements of all participants was taken. Fasting blood samples were taken before and after the intervention-total antioxidant capacity (TAC) of the plasma was measured, total glutathione (GSH) and malondialdehyde (MDA) levels, nitrite/nitrate (NOx) and fasting plasma glucose (FPG) were measured using different methods. The homeostatic model of assessment for insulin resistance (HOMA-IR), the homeostatic model of assessment for beta cell function (HOMA-B), and the quantitative insulin sensitivity check index (QUICKI) were also measured.

Results showed that mean age, height, SBP (systolic blood pressure) and DBP (diastolic blood pressure) were not statistically different between the GSE and placebo groups nor were mean weight and BMI before and after the 8-week intervention period. There was no significant difference found in dietary micro- and macronutrient intake between GSE and placebo groups. There was a significant rise in plasma GSH and significant decrease in MDA and serum insulin concentration levels, HOMA-IR and HOMA-B. GSE had no effect on CPK, TAC, NO, FPG and lipid concentrations compared to placebo. Within-group differences showed a significant decrease in total-/HDL-C in the placebo group. The study showed that administration of GSE for eight weeks in female volleyball players showed beneficial effects on some biomarkers of oxidative stress and insulin metabolism parameters.

References
Delayed Onset Muscle Soreness (DOMS) in Young Healthy Female Students: http://www.sportscienceresearch.com/IJSEHR_201931_03.pdf

Effects of Acute Grape Seed Extract Supplementation on Muscle Damage After Eccentric Exercise: https://www.sciencedirect.com/science/article/pii/S1728869X18303344

Grape Seed Extract Supplementation & the Effects on the Biomarkers of Oxidative Stress & Metabolic Profiles in Female Volleyball Players: http://ircmj.com/en/articles/16766.html

Mankind is inching towards worsening quality of life with the proliferation of disruptive diseases and health problems. Diabetes and infertility are two of the common obstacles faced by many individuals in today’s life. Juvenile diabetes is extremely common these days and a greater number of middle-aged people are victims of type 2 diabetes mellitus (T2DM) owing to inappropriate lifestyle practises and social factors. Fertility rates don’t seem to be positive either-plenty of couples prefer ART methods for conception failing natural conception and there are others who don’t succeed in either. This again, is due to diminishing sperm quality, delayed pregnancies due to career/financial demands and likewise. Statistics show that almost 17% couples seek medical help for fertility treatment indicating deterioration in human reproductive health. This has elicited the attention of researchers and people worldwide on the reasons behind decreasing sperm quality and male fertility rates.

There has been ample discussion on obesity, sedentariness and lifestyle as the key reasons behind decreasing fertility rates in men but the impact of diabetes mellitus (DM) on male reproductive health remains arguable. Worldwide, there are more than 400 million people who suffer from diabetes, both type 1 and type 2. Each of the types has a different history behind its prevalence and brings about different effects on the human body. DM has the ability to garner long-term damage, dysfunction and failure of various organs including loss of vision, renal failure, foot amputation, foot ulcers, cardiovascular symptoms and sexual dysfunction. Diabetes causes substantial effect on the male reproductive system and glucose metabolism is an important event in spermatogenesis. There exists a number of studies, both in animals and humans, that confirm the deleterious effect of diabetes on sexual functions such as semen parameters, nuclear DNA fragments and chromatin quality. Animal models present us with better perspectives in this regard-all of them show decreased fecundity (potential to reproduce). We also have a study which shows that DM is linked to important changes in the metabolomic profile of the testis and a higher percentage of both sperm nuclear and mitochondrial DNA damage.

Diabetes Effect on Epigenetic Regulation of Spermatogenesis
Sperms primarily focus on transferring male haploid DNA to female DNA via a series of mechanisms. Sperm cells are used to trigger fertilization with the female egg and need energy to maintain motion competence after epididymal maturation as they are immobile in the testis. Much adenosine triphosphate (ATP) in sperms is consumed for maintaining this motility. They seek energy mainly in the form of sugar including glucose, fructose and mannose via two metabolic pathways namely anaerobic glycolysis and oxidative phosphorylation. Glucides are polar molecules rich I -OH groups capable of passing the lipidic bilayer in a very slow and inefficient way. An important role of supplying cells with energy is realized by different membrane proteins that can actively (sodium-dependent glucose transporters [SGLT]) or passively (glucose transporters [GLUT]) transport hexose through lipid bilayer. Proteins belonging to SGLT are primary transporters of sugars, especially glucose; proteins of GLUT too transport sugar besides other hexoses such as fructose and mannitol, vitamins and amino sugars. GLUTs mainly function to help the sperm adapt to changes in the environment, metabolic requirements etc but the presence of an abnormal environment such as diabetes can cause dysfunction in nutrient transport leading to decreased fertility rates and adverse foetal outcomes. A study examining GLUT expression of GLUT8 and GLUT9 in sperm and testes in 2 genetically modified diabetic rats showed that rats lacking GLUT9 protein had low sperm motility and decreased fertilization rates. Absence of insulin or hyperglycaemia was the reason behind impaired GLUT9 transcription which shows that insulin and glucose are important to sperm maturation. Treating these mice with insulin showed that sperm motility and concentration improved significantly proving that insulin played a dominant role in sperm quality. The study also showed that it was glucose and not fructose that was needed for fertilization-for sperm oocyte binding and embryo viability in the mouse.

Diabetes Impact on Male Fertility
Type 1 and type 2 diabetes, both affect testicular function and spermatogenesis. Type 1 diabetes brings about structural defects with nuclear and mitochondrial DNA fragmentation, reduced motility and decreased zona pellucida binding in sperm cells. Polyamines in sperms have antioxidant capability, are antiglycating agents and offer protection against structural/functional advanced glycation end products (AGE) modifications. Changes in antioxidant expression could be a triggering factor for oxidative stress (OS) and the number of sperms displaying the receptor for advanced glycation end product (RAGE). The protein content in sperms is normally higher than what is found in the sperm of type 1 diabetic men. Increase in AGE in seminal plasma of type 1 and type 2 diabetic subjects shows that glycation and increased OS play eminent roles in reproductive system dysfunction. Diabetic people suffer from increased levels of RAGE protein and DNA fragmentation in sperms which suggests clearly that RAGE plays a pivotal role in disturbing sexual functionality in diabetic men. Motility rates of these sperms too change owing to alterations in mitochondrial DNA in diabetes.

Researchers have proved that seminal plasma nitrate/nitrite levels and 8-hydroxydeoxyguanosine (8-OHdG) levels are observed to be drastically high in the diabetic group-such high nitrate/nitrite levels must be the work of ROS-induced DNA damage that’s related to 8-OHdG levels but not sperm parameters. But this does not affect sperm motility in any way. On the other hand, malondialdehyde, one of the final products of lipid peroxidation and well-known markers of OS is present in abundance in the semen of infertile men with T2DM and has also been negatively linked to sperm density, total sperm count, progressive motility and normal forms. Controlling glycemic levels in such patients helps in preventing sperm damage. A research by Paasch et al. showed that type 1 diabetes, type 2 diabetes and obesity are accompanied by multiple changes in the sperm proteome.

Absence of normal insulin levels decreases testosterone and Leydig cell function and also FSH, which in turn affects LH levels. Such FSH decrease affects sperm output and fertility. Streptozotocin (STZ) injected in mice for a month showed metabolic adaptations such as increase in efficiency of mitochondrial ATP production. Research shows that fertility rates in the STZ-injected mice were much below than that in the normal group. Even in the fertilized zygotes, embryo development rates to the blastocyst stage in two diabetic models were lower than that in controls. STZ-injected rats also displayed defective sperm maturation and insulin replacement prevented these changes partially or completely.  

Impact of Diabetes on Assisted Reproduction Treatment (ART)
A research set forth to analyse whether presence of diabetes in men affected ART outcomes. Men who reported as diabetic the first time they visited the centre for fertility treatment were considered for the study. Information fetched was split into three data stream which included male, female and assisted reproduction treatment. Information regarding date of birth, diabetes type and duration, smoking status and nature of the treatment was recorded for men. Sperm data regarding volume of ejaculate, sperm concentration and extent of liquefaction were also noted. In the case of female, information on number of cycles, number of eggs harvested, number fertilized, whether embryos were frozen and other clinical outcomes were measured. There were 80 couples among whom 18 diabetic men (aged 28-51 years) and their partner (aged 24-41 years) had undergone assisted reproductive treatment between 2004 and 2007.

Reasons for infertility was attributed to idiopathic male factor for 4 couples, polycystic ovary syndrome for 2 couples, unexplained causes for 10 couples, hyperprolactinaemia for one couple and endometriosis for one couple. While it was the first child for all female participants one subject had three previous miscarriages and another one had suffered from one miscarriage. On an average, men had suffered from diabetes for around 17 years. 38% reported that their levels were well-controlled, 27% told that it was poorly controlled and the other 35% reported that they were unaware of the status. Of the 18 diabetic males, 2 (11%) of them had retrograde ejaculation and two were azoospermic, none of them tested positive for antibody presence, liquification was normal for 13 subjects, reduced motility was present in 80% subjects and 60% showed decrease in percentage of normal forms.
Of the 18 couples who opted for ART 5 of them underwent 10 circles of IVF, 12 underwent 19 cycles of intracytoplasmic sperm injection (ICSI) and one couple underwent two cycles of IVF and one cycle of ICSI. 5 couples who started with ICSI opted for frozen embryo transfer (FET) (seven cycles). For IVF, a 68% fertilization rate was possible for 66 harvested eggs. In spite of 12 embryo transfers there was no signs of pregnancy. In the case of ICSI a fertilization rate of 62% was achieved for 198 harvested eggs. Here, despite 18 embryonic transfers there was only one clinical pregnancy represented and a combined IVF/ICSI clinical pregnancy rate per embryo transfer of 3.3% for fresh cycles occurred. FET showed better outcomes with 29% clinical pregnancy rate and no miscarriage or complications were present in any of the deliveries.

Type 1 & Type 2 Diabetes Effects on Sperm Quality
Here, study participants were divided into three groups-38 patients with DM1, 55 with DM2 and 100 healthy fertile subjects as controls. DM1 patients were further divided into three groups depending on the duration of the disease- <5 years, between 5 and 10 years and >10 years. All the participants underwent a sperm analysis, a flow cytometric sperm analysis, assessment of the presence of urogenital infection, oxidative stress evaluation and an andrological evaluation. Sperm parameters showed considerable difference between the three groups. Individuals with DM1 and DM2 showed decreased sperm concentration compared to controls while DM2 participants showed slightly lower sperm quality compared to DM1 individuals. Motility rates were lower in DM1 and DM2 individuals compared to controls, much lower in DM1 compared to DM2. Semen fluid volume was comparatively lower in patients with DM1 though not much significant in DM2 participants when compared to controls. Sperms having normal forms were in lower percentage compared to controls. Sperm vitality decreased in DM2 participants and one patient had higher degree of DNA fragmentation spermatozoa compared to DM1 patients and controls.

This study showed that type 1 diabetes patients have low ejaculate volume due to increased oxidative stress which can also alter other conventional sperm parameters. Type 2 diabetes patients suffer from increased concentration of seminal fluid leukocytes that raise OS levels damaging sperm parameters, sperm DNA and vitality.

All these show that glucose metabolism plays a pivotal role in sperm cells and any type of diabetes could have detrimental effects on male fertility, specifically sperm quality.

References
Diabetes Mellitus & Infertility: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5980990/pdf/fendo-09-00268.pdf

Male Diabetes Mellitus & Assisted Reproduction Treatment Outcome: https://www.rbmojournal.com/article/S1472-6483(10)00652-8/pdf

The Effects of Diabetes on Male Fertility & Epigenetic Regulation During Spermatogenesis: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4814953/pdf/AJA-17-948.pdf