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Access to and adequate consumption of a variety of colorful, nutrient-dense foods are important components of chronic disease treatments as well as preventative and optimal health strategies. Personalized dietary approaches that emphasize the consumption of plants (e.g., fruits, vegetables, whole grains, spices, nuts, and seeds), quality proteins, and healthy fats over the intake of highly processed foods help support metabolic health and function. From sugars to starches to fiber, carbohydrates are important macronutrients in the human diet. Complex carbohydrates and simple sugars supply the body with glucose, which in turn is converted to energy. But not all carbohydrates deliver the same metabolic impact and nutrient density.^1,2 Minimally processed foods may offer a healthier source of carbohydrates that provides vitamins, minerals, fiber, prebiotics, and phytonutrients, unlike the high-glycemic foods common in the Western-pattern diet such as prepackaged meals, refined grains and cereals, and high-sugar drinks.

Studies continue to research the optimal levels of overall carbohydrate intake for specific populations, and many clinical trials have found that ketogenic and reduced-carbohydrate diets may be beneficial for patients with a range of chronic diseases, including obesity, type 2 diabetes, and metabolic syndrome.^3-6 Other randomized clinical trials have also researched reduced-carbohydrate dietary approaches on populations from athletes to non-athlete adults within normal BMI ranges and without metabolic disorders, also reporting potential benefits such as enhancing insulin sensitivity^7,8 and reducing inflammatory biomarkers and triglycerides.^9,10

As this area of research expands with additional clinical trials, a new observational study explored low-carbohydrate intake for adults with normal BMI and no diagnosis of cardiometabolic dysfunction.¹¹ The results suggested that low-carbohydrate diets such as the ketogenic diet negatively impact glucose homeostasis and inflammation in this population.¹¹ As these observational study results do not necessarily align with some clinical trials published in this area of research, several factors are important to note when interpreting the results of this study, as described below. Ultimately, consideration of social and lifestyle factors, environmental exposures, nutritional status, and total dietary intakes are all vital to understanding a patient’s glucose and insulin-related biomarkers and their overall metabolic health.

New Study Exploring Low-Carb Intake

Recently, the 2023 Al-Reshed et al cross-sectional study investigated the short-term health impact of low-carbohydrate consumption measured by inflammatory and metabolic biomarkers.¹¹ For seven days, 120 participants who lived in Kuwait and did not have a history or current diagnosis of cardiometabolic dysfunction (mean age of 31.9; BMI=/<25 kg/m²; 63 women) used a food diary to track their normal dietary intake. Their physical activity was measured by an electronic accelerometer. Blood samples were also collected. Based upon the analysis of the food diaries, participants were divided into three groups according to their carbohydrate consumption level:¹¹

• The low carbohydrate group (n=38) consumed less than 45% of their daily energy intake from carbohydrates.
• The recommended range of carbohydrate group (n=62) consumed 45-65% of their daily energy intake from carbohydrates, which follows the acceptable macronutrient distribution range (AMDR) found in the US Dietary Guidelines for carbohydrate consumption.
• The high carbohydrate group (n=20) consumed more than 65% of their daily energy intake from carbohydrates.

Among their results, investigators reported that the low carbohydrate group (LCG) was significantly associated with higher levels of insulin resistance measured by HOMA-IR and C-peptide levels compared to the recommended range of carbohydrate group (RCG). Further, the C-peptide elevation in the LCG was found to be associated with the secretion of inflammatory markers. The LCG also reportedly displayed significantly lower serum bicarbonate and serum albumin levels than the RCG. Investigators noted that these lower levels are considered signs of metabolic acidosis. The researchers concluded that this was the first study to suggest that low carbohydrate consumption by “healthy” individuals with normal BMI may negatively impact glucose metabolism and increase metabolic acidosis and inflammatory parameters.¹¹

Considering Potential Biases and Confounders

When reflecting on this study’s conclusions, some important considerations include the small sample size of participants reporting a low-carbohydrate diet, the population of only people living within Kuwait, and the brief seven-day food recall used to establish a dietary pattern. These factors may impact the generalizability and reproducibility of the study results. In addition, the self-reported food diary may have introduced a study bias. Also of important note, participants included in this study were recognized as “healthy” because they did not have an official metabolic disorder diagnosis and were within a normal BMI range; however, BMI may not be a reliable indicator of optimal metabolic health. In fact, US reports indicate that the prevalence of metabolically healthy adults is low,¹² even for those within a normal BMI range.¹³

While the researchers acknowledged some of these potential limitations, other possible confounders were not mentioned and may have influenced the results. Lifestyle and environmental factors may present confounders in this study. Researchers noted that the physical activity amounts did not vary significantly between groups; however, researchers did not include other potentially confounding factors for the study population such as socioeconomic status, smoking habits, and environmental toxicant exposures, all of which have been suggested to impact metabolic health.^14-18

vital considerations: Nutritional Status & Dietary Patterns

Complete diet composition and dietary habits were not recorded for the participants in this study. Only total calories and carbohydrates were measured, recorded, and used for analysis. The types and quality of carbohydrates consumed (e.g., fiber, simple sugars, nutrient density, etc.) were not distinguished. Also, no other macronutrients or nutritional patterns (e.g., healthy fats, quality proteins, intake of plants versus intake of meats, timing of meals, etc.) were recorded. Other research studies have indicated that complete nutritional patterns are essential for more informative assessment of health impacts.¹⁹

Interestingly, the researchers in this study used the 2018 Seidelmann et al cohort study on low-carbohydrate intake and mortality to affirm their observation of a U-shaped effect of more potential negative health impacts seen in both the low and high-carbohydrate intake groups. However, researchers did not mention that while the overall results of the 2018 Seidelmann et al study did indicate that both low and high-carbohydrate consumption conferred greater mortality risk than moderate-carbohydrate intake, further analysis indicated that those results varied by the source of the exchanged macronutrients. Investigators in the 2018 Seidelmann et al study found that participants who replaced carbohydrates with plant-based substitutions decreased mortality risk while animal-derived fat and protein substitutions were associated with an increased mortality risk.¹⁹ Relevant to low-carbohydrate diets, studies that have considered the type of fat consumed (i.e., saturated, polyunsaturated, monounsaturated, etc.) have suggested that substitution of carbohydrates by mainly saturated fats may negatively impact lipid profiles²⁰ while replacing carbohydrates with poly or monounsaturated fats may improve lipid profiles to support metabolic health.²¹

In the 2023 Al-Reshed et al study, the LCG and RCG had similar total calorie intakes; therefore, highlighting the carbohydrate substitutions would be important for a more complete assessment. This would be extremely important for this Kuwait-specific population due to recent reporting that suggested a link between suboptimal dietary intake patterns (i.e., low intake of fruits, vegetables, nuts, seeds, and whole grains and high intake of sodium and sugar-sweetened beverages) and a substantial proportion of cardiometabolic deaths in Kuwaiti adults.²² Understanding the complete dietary patterns of participants in addition to assessing any micronutrient deficiencies or insufficiencies would add needed context when interpreting biomarker testing. In addition, the timing of carbohydrate consumption may also play a role in metabolic health and may also influence glucose and insulin-related biomarker testing, as seen in previous research.^5,23

Conclusion

While the Al-Reshed et al study continues the important diet and health conversation, the title and conclusions in this cross-sectional study are extremely misleading when many lifestyle, demographic, and nutritional factors were not recorded, assessed, or available for consideration.

From a functional medicine perspective, understanding the array of factors that may impact an individual patient’s complete health story is vital for both disease treatment and preventative interventions and when determining if a reduced-carbohydrate diet is appropriate as part of a wellness strategy. For example, access to quality, nutrient-dense food choices, health and nutrition literacy, and other social determinants of health may impact overall quality of an individual’s dietary pattern. A patient’s daily environmental exposures, from pollutants to psychosocial stressors, may play a role in glucose homeostasis and contribute to metabolic health. Considering the entirety of these factors and emphasizing a rainbow of nutrient-dense, plant-based foods to ensure the adequate intake of a variety of healthy micro and macronutrients are core components when developing a personalized approach to optimal health and wellness.

Related Articles

Type 2 Diabetes and Ketogenic Diet

Endocrine Disruptors and Type 2 Diabetes

Food First: Dietary Change Improves Outcomes

Chrononutrition: Food Timing, Circadian Fasting, and the Body’s Internal Clock

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