I’m skeptical about … ketogenic diets.

The quote “Let food be thy medicine and medicine be thy food” is attributed to Hippocrates, who lived more than 2 millennia ago. It seems equally true today judging from the plethora of fad diets, food crazes, and miracle nutrients that are continually promulgated into the collective psyche of the American public in its elusive quest for thinness and wellness. The ultra-low-fat diet, proposed by Dr. Dean Ornish 4 decades ago, to combat cardiovascular disease has largely given way to the ultra-low-carbohydrate diet, first made popular by Dr. Robert Atkins, and since taken up by science writers like Gary Taubes (Why We Get Fat and The Case Against Sugar), not to mention countless CrossFit, paleo aficionados. Nearly 80% of Americans now view carbs negatively, a huge jump from 20 years ago. Carbs are out. Keto is in.

 

 

First, a word or two about diets. Diets consist of macronutrients, micronutrients, and water. Macronutrients are comprised of: 1) Carbohydrates, that include both starches and simple sugars; 2) Proteins, composed of linked amino acids, the primary component of muscle, and; 3) Fats that include cholesterol, fatty acids, and triglycerides.

Micronutrients include 14 vitamins (essential chemicals that, with the exception of niacin and vitamin D3, cannot be synthesized by the body), and a host of minerals like calcium, magnesium, sodium, and potassium. Foods also contain probiotics, prebiotics, phytochemicals, and a bunch of other ingredients, all of which are chemicals, many of them toxic (e.g. muscarine and phallotoxin in mushrooms). All food is chemical in nature, and just as there is nothing inherently “safe” about organic foods, there is also nothing inherently “unsafe” about genetically modified foods. In fact, almost everything we eat has been genetically modified in one way or another to improve taste, enhance specific flavors, eliminate toxins, or extend shelf-life (think seedless grapes, burpless cucumbers, and sweet corn—all delicious and all genetically modified).

The amount of water an individual requires varies markedly from person-to-person and from day-to-day, depending on activity, perspiration rate, ambient outdoor temperature and humidity levels. The kidneys, colon, lungs, and sweat glands all have roles to play in maintaining fluid balance, and there is not much truth to the standard recommendation to drink eight 8-ounce glasses of water daily. In general, the amount of water you need—assuming normal kidney function—is whatever it takes to quench thirst and produce a plentiful amount of clear urine (an exception being in diabetics where excessive urination is a sign of elevated blood sugar). Despite what the sports beverage industry would have you believe, nothing hydrates better than water. On hot, humid days during long workouts, athletes may require several gallons of water to replace fluid losses, while a thin, indoor, sedentary person may require as little as 40-50 ounces per day. In the absence of excessive losses, staying hydrated isn’t a problem for most of us.

Now for a bit of physiology. The number of calories required to keep the show running depends on a person’s age, sex, body composition, and activity level. The BMR (basal metabolic rate) is the energy required at rest to maintain vital functions like temperature control, breathing, circulation, digestion, and cell growth. A simple approximation of BMR is weight (kg) x 23.9 Cal/day. This accounts for 60-75% of caloric needs. Note that muscle, even at rest, burns more calories than fat. Thus, all other things being equal, an individual with 10% body fat will burn more calories at rest and have a higher BMR than someone with 40% body fat (another reason to incorporate weight training into your fitness routine).

Activity accounts for the remainder of a person’s daily caloric needs. Women typically require between 1,600-2,400 calories/day while men need more, between 2,000-3,000 calories/day. Unfortunately, according to the UNFAO (United Nations Food and Agriculture Organization), Americans are now consuming roughly 3,600 Cal/day. Currently, more than a third of adult Americans are obese, a number expected to jump to half by 2030 if current trends continue. No diet works without cutting calories. The holy grail lies in determining which calories to cut in order to most efficiently lose weight without harming the body. Should you cut carbs, fats, proteins, or all 3 equally?

 

Dietary Macronutrient Composition and Daily Calories Over Time (www.ourworldindata.org)

 

 

The average American diet derives 45-50% of its total daily calories from carbohydrates (starches and sugars), 15-20% from proteins, and 35-40% from fats. Low-carbohydrate diets strive to incorporate less than 30% of total calories from carbohydrates, while very-low-carbohydrate diets (ketogenic diets) shoot for just 5-10% of calories from carbs. Alternatively, the goal of low-fat diets is to consume less than 30% of total calories from fat, with very-low fat diets dropping that number down to less than 10% fat calories. Both very-low-carbohydrate and very-low-fat diets have enthusiastic proponents and detractors. Both promote weight loss, but is one healthier than the other, and are either healthier than simply eating a balanced diet of fewer calories (e.g. Mediterranean diet)?

 

Macronutrient Metabolism

 

Under usual circumstances, the body preferentially utilizes glucose as its primary energy source. Carbohydrates are broken down into simple sugars in the gut, absorbed, and transported to the liver and muscle, where they are taken up and stored for later use. Insulin is required for this process, and its absence leads to the accumulation of glucose in the bloodstream that is unavailable for energy production and ultimately excreted in the urine. It’s also important to note that not all sugars are stored as glycogen (a polymer of glucose). For example, fructose, plentiful in fruits and all things sweetened with fructose corn syrup, is converted primarily to fat.

In times of carbohydrate shortage, the body necessarily turns to alternative sources of energy. Without metabolic redundancy systems, the body would soon find itself in significant turmoil during times of extended exercise or food shortage. Fortunately, humans are readily capable of utilizing both proteins and fat for energy production. Proteins, first catabolized to amino acids, can be converted to sugar in a process known as gluconeogenesis. Fats, in the form of triglycerides, can be catabolized to glycerol (converted to glucose) while the fatty acid components are further metabolized to acetyl-CoA (the primary substrate for energy production via the Krebs cycle). The conversion of both proteins and fats comes with a cost, however, in the form of ketones.

 

Ketone Bodies (Acetoacetate, Beta-Hydroxybutyrate, Acetone)

 

The process of ketosis, from which the ketogenic diet derives its name, needs to be distinguished from ketoacidosis, seen in diabetics, starvation states, and after specific toxic ingestions. Ketosis represents a normal physiologic process, whereas ketoacidosis is always pathologic, representing an extreme, life-threatening disturbance in metabolism. In the ER, patients with ketoacidosis are admitted to the ICU, whereas a person with physiologic ketosis secondary to a ketogenic diet might be running next to you in a 10K race. In the setting of adequate hydration, fat calories, and protein calories, the ketosis induced through the intentional dietary restriction of carbohydrates does not result in acidosis, or even a significant drop in blood sugar (glucose) levels. The nuance lies in converting the body’s metabolism to a fasting state without actually starving it.

It needs to be stressed again that the primary way ketogenic diets work is through calorie restriction. No calorie restriction, no weight loss. The argument of ketogenic proponents, however, is that the diet works better than other diets utilizing similar calorie restriction. There are several reasons why this might be true. The brain prefers glucose but, in a pinch, can utilize ketones for energy. At a minimum, the body utilizes 60-65 gm. of glucose (240-260 calories worth) daily and, in the absence of dietary carbohydrate, the body produces it via gluconeogenesis and fat conversion, at a cost of roughly 400-600 calories. Although metabolically inefficient, this extra expenditure of calories can be used to advantage when trying to lose weight.

 

(Exercise Sport Sci Rev 2015; 93: 153.)

 

Second, there is evidence that ketosis directly suppresses appetite by altering hormonal signals to the brain (leptin and ghrelin). This makes sense from an evolutionary standpoint, given that, under normal circumstances, significant ketosis only occurs during times of food shortage. The brain is essentially “tricked” into appetite suppression. There is also evidence that high protein diets—a necessary consequence of eating fewer carbs—diminishes appetite via a separate hormonal system (cholecystokinin and peptide YY). People on ketogenic diets typically report less hunger, despite consuming fewer calories, a major plus when it comes to weight loss.

Third, ketogenic diets that severely restrict carbohydrates improve insulin sensitivity in both diabetic and non-diabetic patients, resulting in lower blood glucose levels and lower hemoglobin A1c levels. Insulin-mediated fat metabolism improves as well. Since insulin is primarily a “storage hormone” that promotes the uptake of both sugar and fat, as insulin sensitivity improves the signal for fat formation declines and counter signals for fat breakdown are enhanced. The net result is a decline in fat.

So far, so good. Everything seems to favor ketogenic diets over other forms of calorie restriction. So why am I skeptical? First, here’s a partial list of things you won’t be eating while on a ketogenic diet: bread, barley, pasta, rice, potatoes, oats, carrots, beets, beans, peas, corn, granola bars, crackers, cereal, oatmeal, pizza, popcorn, apples, oranges, peaches, bananas, watermelon, cherries, grapes, mango, pineapple, cakes, cookies, pastries, pudding, pie, ice cream, chocolate, table sugar, sweetened sodas, fruit juices, or alcohol of any kind. It’s not easy. Sure, go ahead and have that steak and salmon, but no bread to go with it and no dessert. Meats, eggs, and full fat milk are encouraged. This is decidedly not a vegan friendly diet. In general, vegetables that grow above ground, like avocados, cauliflower, cabbage, lettuce, broccoli, and asparagus are okay in moderation, while those that grow below ground (root vegetables) are out. About the only fruits allowed are a spattering of berries (strawberries, raspberries, and black berries with an occasional blueberry tossed in). Most nuts are okay, with the exception of cashews and pistachios, but remember that nuts are extremely calorie dense, with an ounce of almonds (24 nuts) setting you back 160 calories and an ounce of pecans (15 halves) tipping the scale at nearly 200 calories.

 

Ketogenic Food Pyramid (Baltimore Post-Examiner, 4/17/2018)

 

But let’s say you decide to take the plunge anyway because everybody is doing it and swearing by the results. Early on, don’t expect to feel well. Known as the “keto flu,” most people experience a generalized sluggishness and malaise often accompanied by GI irritability, nausea, headache, muscle cramps, loss of mental focus, sleep disruption, and sugar cravings. These symptoms are most prominent early on as ketone levels reach their peak. Since each gram of glucose stored as glycogen also stores 3 grams of water, the glycogen depletion associated with ketogenic diets also leads to water depletion, so staying well hydrated helps (let the color and volume of urine be your guide). Minerals, especially potassium and magnesium, may also be lost leading to muscle cramps, so eating mineral-dense foods like avocados, almonds, and spinach may help some. Symptoms typically subside over 10-14 days as the body adapts and ketone levels decline. This is not the time to try to set a personal best in any athletic endeavor.

 

Serum Ketone Concentration (Beta-Hydroxybutyrate) Over Time, Low-Carbohydrate vs High-Carbohydrate Diet (Am J Clin Nutr 2009; 90: 23.)

 

Here’s the good news: You will lose weight! And, the not-so-good news: You won’t lose any more than you would on another diet of similar calorie restriction. Despite the above-mentioned theoretical reasons why ketogenic diets might work better, actual practice doesn’t bear this out. The majority of trials, including several meta-analyses, have found no difference in long term weight loss with ketogenic diets versus other diets of similar calorie restriction. In both, adherents tend to shed between 11-16 pounds, which is still quite impressive.

Ketogenic diets work, but are they healthy? There is a lot of data to support the notion that fat restriction (not fat supplementation) is beneficial to cardiovascular health. Both the National Institutes of Health and the American Heart Association recommend diets containing no more than 30% of total calories from fat (with no more than 10% coming from saturated fats). Meanwhile, most ketogenic diets result in nearly twice that percentage of fat calories. The data comparing very-low-fat versus very-low-carbohydrate diets on metabolic markers has yielded fairly consistent results. Both diets demonstrate similar declines in weight, blood sugar, and blood pressure, as well as overall improvement in lipid profiles, but the effect on the individual components of those profiles differs. In general, very-low-fat diets result in slightly larger declines in total cholesterol and LDL-cholesterol (“bad” cholesterol) compared to very-low-carbohydrate diets, but less of a decline in triglycerides and less of an increase in HDL-cholesterol (“good” cholesterol). This is confusing and somewhat counter-intuitive, but when considering the “total cholesterol to HDL ratio,” a commonly used predictor of cardiovascular disease risk (optimum ratio 3.5), both diets perform similarly. Although there are many inherent flaws in the design of observational dietary trials, the data suggests that ketogenic diets are likely as safe as other diets when it comes to the risk of cardiovascular disease. Both low-carb (Atkins) and low-fat (Ornish) diets reduce risk, but it’s the total amount of weight lost that seems to count most. The more, the better. In patients with metabolic syndrome or diabetes, weight loss improves virtually every measurable metabolic parameter, including markers of “inflammation.”

If you’re contemplating a ketogenic diet, know also that there is strong observational data, both from the Nurses Health Study (more than 80,000 patients) and the Health Professionals’ Follow-Up Study (more than 50,000 patients), suggesting that people on low-carbohydrate diets consuming fat and protein primarily from plant-based sources have lower cardiovascular and overall mortality relative to those who receive most of their fat and protein from animal sources. The advice here is clear; no matter which diet you choose, results are better when consuming plants over animals.

A final note to athletes: The majority of data suggests that neither strength nor endurance declines while on a ketogenic diet. Whether ketosis enhances performance remains unsettled, or as one article put it: “The use of ketogenic diets in sports is still a twilight zone ‘the middle ground between light and shadow, between science and superstition.’” Although the Internet is replete with glowing testimonials, remember that anecdotal evidence is not science. While weight loss may be readily quantifiable, athletic performance depends upon a host of confounding variables, and it’s entirely possible that the benefit of “going keto” is mostly, or entirely, a placebo effect. Regardless, keep exercising, as all diets work better when augmented with a work-out.

 

(Exercise Sport Sci Rev 2015; 93: 153.)

 

 

Bottom Line: Although associated with unpleasant short-term side effects, ketogenic diets work to promote weight loss. In the aggregate, they do not work better than other diets of similar calorie restriction. Ketogenic diets likely do not increase the risk of cardiovascular disease. It remains uncertain if athletic performance is enhanced through their use.

 

References:

  1. Antonio Paoli et al., “Beyond Weight Loss: A Review of the Therapeutic Uses of Very-Low-Carbohydrate (Ketogenic) Diets,”  Eur J Clin Nutr 2013; 67: 789-96.
  2. J. Acheson, “Diets for Body Weight Control and Health: The Potential of Changing the Macronutrient Composition,” Eur J Clin Nutr 2013; 67:462-66.
  3. Antonio Paoli, “Ketogenic Diet: Friend or Foe?” Internat’l J Environ Res and Pub Health 2014; 11: 2092-2107.
  4. Sumithran et al., “Ketosis and Appetite Mediating Nutrients and Hormones After Weight Loss,” Eur J Clin Nutr 2013; 67: 759-64.
  5. Davidenko et al., “Control of Protein and Energy Intake—Brain Mechanisms,” Eur J Clin Nutr 2013; 67: 455-61.
  6. A. Gibson et al., “Do Ketogenic Diets Really Suppress Appetite? A Systematic Review and Meta-Analysis,” Obesity Rev 2015; 16: 64-76.
  7. Carol Johnston et al., “Ketogenic Low-Carbohydrate Diets Have No Metabolic Advantage over Nonketogenic Low-Carbohydrate Diets,” Am J Clin Nutr 2006; 83: 1055-61.
  8. Grant Brinkworth et al., “Long-Tern Effects of a Very-Low-Carbohydrate Weight Loss Diet Compared with an Isocaloric Low-Fat Diet After 12 Months,” Am J Clin Nutr 2009; 90: 23-32.
  9. Tian Hu et al., “Effects of Low-Carbohydrate Diets Vs. Low-Fat Diets on Metabolic Risk Factors: A Meta-Analysis of Randomized Controlled Trials,” Am J Epid 2012; 176(s): s44-s54.
  10. Nassib Bueno et al., “Very-Low Carbohydrate Ketogenic Diet Versus Low-Fat Diet for Long-Term Weight Loss: A Meta-Analysis of Randomized Controlled Trials,” Brit J Nutr 2013; 110: 1178-87.
  11. Thomas Halton et al., “Low-Carbohydrate-Diet Score and the Risk of Coronary Heart Disease in Women,” NEJM 2006; 355: 1991-2002.
  12. Lukas Schwingshackl and Georg Hoffmann, “Comparison of Effects of Long-Term Low-Fat vs High-Fat Diets on Blood Lipid Levels in Overweight or Obese Patients: A Systematic Review and Meta-Analysis,” J Acad Nutr Diet 2013; 113: 1640-61.
  13. Terea Fung et al., “Low-Carbohydrate Diets and All-Cause and Cause-Specific Mortality: Two Cohort Studies,” Ann Int Med 2010; 153: 289-98.
  14. Chen-Kang Chang et al., “Low-Carbohydrate-High-Fat Diet: Can It Help Exercise Performance?” J Hum Kinetics 2017; 56: 81-92.
  15. Antonio Paoli et al., “The Ketogenic Diet and Sport: A Possible Marriage?” Exercise Sport Sci Rev 2015;93(3): 153-62.

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