When somebody loses weight, where does the fat go?

Introduction

- A widespread misconceptions about how humans lose weight among general practitioners, dietitians, and personal trainers was found.

- Most people believed that fat is converted to energy or heat, which violates the law of conservation of mass.

- We suspect this misconception is caused by the “energy in/energy out” mantra and the focus on energy production in university biochemistry course

- Other misconceptions were that the metabolites of fat are excreted in the faeces or converted to muscle.

- The complete oxidation of a single triglyceride molecule involves many enzymes and biochemical steps, but the entire process can be summarised as:

C₅₅H₁₀₄O₆+78O₂→55CO₂+52H₂O+energy

- Stoichiometry shows that complete oxidation of 10 kg of human fat requires 29 kg of inhaled oxygen producing 28 kg of CO₂ and 11 kg of H₂O.

  

Novel Calculation

The proportion of a triglyceride molecule’s mass exhaled in CO₂ is the proportion of its molecular weight (daltons) contributed by its 55 carbon atoms plus four of its oxygen atoms:

(661 Da (C₅₅)+64 Da (O₄))/(861 Da (C₅₅H₁₀₄O₆))×100=84%

The proportion of mass that becomes water is:

(105 Da (H₁₀₄)+32 Da (O₂))/(861 Da (C₅₅H₁₀₄O ))×100=16%

- These results show that the lungs are the primary excretory organ for weight loss (fig 2).

- The water formed may be excreted in the urine, faeces, sweat, breath, tears, or other bodily fluids

Lifting the veil on weight loss

- At rest, an average 70 kg person consuming a mixed diet (respiratory quotient 0.8) exhales about 200 ml of CO₂ in 12 breaths per minute

- Each of those breaths therefore excretes 33 mg of CO₂, of which 8.9 mg is carbon.

- In a day spent asleep, at rest, and performing light activities that double the resting metabolic rate, each for 8 hours, this person exhales 0.74 kg of CO₂ so that 203 g of carbon are lost from the body.

- For comparison, 500 g of sucrose (C₁₂H₂₂O₁₁) provides 8400 kJ (2000 kcal) and contains 210 g of carbon.

- Replacing one hour of rest with exercise that raises the metabolic rate to 7 times that of resting by, for example, jogging, removes an additional 39 g of carbon from the body, raising the total by about 20% to 240 g.

- For comparison, a single 100 g muffin represents about 20% of an average person’s total daily energy requirement.

- Physical activity as a weight loss strategy is, therefore, easily foiled by relatively small quantities of excess food.

Conclusions

- Our calculations show that the lungs are the primary excretory organ for fat.

- Losing weight requires unlocking the carbon stored in fat cells, thus reinforcing that often heard refrain of “eat less, move more.”

Meerman& Brown. BMJ 2014;349:g7257

Body-Mass Index in 2.3 Million Adolescents and Cardiovascular Death in Adulthood

AIM

- To investigate the association between body mass index (BMI) in late adolescence and death from cardiovascular disease in adulthood.

METHOD

-BMI data from 1967 through 2010 Israeli adolescents (mean age 17.3±0.4 years) were grouped according to age- and sex- specific percentiles from the US CDC.

[Underweight: <5^th percentile

Normal weight: 5^th to 24^th percentile (Reference group), 25^th to 49^th percentile, 50^th to 74^th percentile, 75^th to 85^th percentile

Overweight: 85^th to 94^th percentile

Obese: ≥ 95^th percentile]

- Total number of study sample: 2,298,130 participants

- Primary outcomes: number of deaths attributed to coronary heart disease, stroke, sudden death from unknown cause or a combination of all three categories (total cardiovascular causes) by mid-2011.

- Statistical analysis: Cox proportional-hazards models; imputed 1.4% of missing values (country of origin, education and socioeconomic status) using multiple imputation algorithm; applied linear and quadratic terms using the midpoint of each BMI percentile group or the median of each absolute BMI group; spline models were fit to estimate the BMI value associated with minimum cardiovascular mortality and the lowest BMI associated with significantly increased mortality.

RESULTS

- During 42,297,007 person-years of follow-up, 2918 of 32,127 deaths (9.1%) were from cardiovascular causes, including 1497 from coronary heart disease, 528 from stroke, and 893 from sudden death.

- The mean ages at the time of death were 47.4 years for coronary heart disease, 46.0 years for stroke, and 41.3 years for sudden death

- The rates of death per person-year were generally lowest in the group that had BMI values during adolescence in the 25th to 49th percentiles, with higher rates observed among those below the 5th percentile.

- A graded increase in the risk of death from cardiovascular causes and all causes that started among participants in the group that was in the 50th to 74th percentiles of BMI (i.e., within the accepted normal range).

Analysis based on percentile grouping

Hazard ratio after multivariable adjustment* (Reference group: 5^th to 24^th percentile):

- Overweight (85^th to 94th percentiles): 3.0 (95% CI, 2.5-3.7) for death from coronary heart disease, 1.8 (95% CI, 1.3-2.5) for death from stroke, 1.5 (95% CI, 1.1-1.9) for sudden death, and 2.2 (95% CI, 1.9-2.6) for death from total cardiovascular causes

-Obese group (≥95^th percentile for BMI): 4.9 (95% CI, 3.9-6.1) for death from coronary heart disease, 2.6 (95% CI, 1.7-4.1) for death from stroke, 2.1 (95% CI, 1.5-2.9) for sudden death and 3.5 (9.5% CI, 2.9-4.1) for death from total cardiovascular causes

*(adjustment for sex, age, birth year, sociodemographic characteristics, and height)

Analysis based on year of follow-up

- Hazard ratio from death from cardiovascular disease increased from 2.0 (95% CI 1.1 to 3.9) during follow-up for 0 to 10 years to 4.1 (95% CI 3.1 to 5.4) during follow-up for for 30 to 40 years

- The risk was persistently high for death from coronary heart disease across the entire period of follow-up.

Analysis of absolute values of BMI

- Participants with a BMI ranging from 20.0 to 22.4 had a higher risk of death from coronary heart disease than did those with a BMI ranging from 17.5 to 19.9 (hazard ratio, 1.2; 95% CI, 1.1-1.4)

- The risks of death from stroke, sudden death, and total cardiovascular causes (along with noncardiovascular causes and all causes) were also elevated starting with a BMI of 22.5 and increased more steeply among the extremely obese for cardiovascular-specific death

On multivariable-adjusted spline models,

-The minimum risks of death from stroke, sudden death, and cardiovascular causes were among participants who had BMI values of 19.8, 19.3, and 18.3, respectively, whereas the association with death from coronary artery disease was graded across the full range of BMI-percentile groups

- Participants had a significantly elevated risk of death from total cardiovascular causes starting at BMI values above 20.3.

Analysis by z-scores of BMI

- After multivariable adjustment, the hazard ratios for death from coronary heart disease were 1.54 (95% CI, 1.46 to 1.62) for men and 1.58 (95% CI, 1.31 to 1.91) for women per 1-unit increment in the z score

Sensitivity analysis

- Findings persisted in extensive sensitivity analyses: sex-specific, restricted to adolescents with unimpaired health status, analysis modelling the association without competing risks that used the group with BMI values in the 25th to 49th percentiles as the reference category, restricted to participants who were evaluated after 1981 and to those who were evaluated from 1967 through 1980, comparing deaths that occurred before the age of 45 years with those that occurred at the age of 45 years or older, analyses according to calendar periods of follow-up and country of origin, and an analysis that included all cardiovascular diseases defined according to ICD coding (9.9% of all deaths)

Analysis of population-attributable fractions

- Among participants with a BMI higher than the 50th percentile in 2013, the projected population-attributable fractions were 28% for death from total cardiovascular causes and 36% for death from coronary heart disease

DISCUSSION

- There is a graded increase in the risk of death starting at the mid-normal range of adolescent BMI (50th to 74th percentiles) and that the high normal BMI range (75th to 84th percentiles) was associated with hazard ratios of 2.2 for coronary heart disease and 1.8 for total cardiovascular causes.

- Our findings appear to provide a link between the secular trends in adolescent overweight and coronary mortality during the past decades. In contrast to the steep decline in the rate of death from cardiovascular causes among older age groups, cardiovascular mortality among young adults has not decreased or the decline has slowed in several developed countries.

LIMITATIONS

- Absence of adult measures of BMI, an independent effect of adolescent BMI on death from cardiovascular disease in adulthood cannot be assessed.

- Unable to account for important cardiovascular lifestyle risk factors (such as smoking, exercise, and physical fitness) that may confound the BMI association, although adjustment for smoking had no effect in other studies, and a mendelian randomization study showed effects for BMI that were independent of confounding

- The study sample is less representative of Israeli women, and the findings need to be confirmed in a racially and ethnically diverse population

CONCLUSION

- An increased BMI in late adolescence, even within the currently accepted normal range, was strongly associated with cardiovascular mortality in young adulthood or midlife

- We could not determine whether an increased BMI in adolescence is an independent risk factor, is mediated by adult obesity, or both

Twig et al. N EnglJ Med 2016; 374:2430-2440. DOI: 10.1056/NEJMoa1503840

Low energy intake plus low energy expenditure (low energy flux), not energy surfeit, predicts future body fat gain

The energy surfeit theory, which is commonly apply in weight management, emphasized to attain negative energy balance (Energy expenditure > Energy Intake) for weight reduction.

However, this weight reduction is not always sustainable (most people who used a reduced-calorie weight loss strategy regain the lost weight).
Maintaining high energy flux (high energy intake and expenditure) may induces metabolic changes that are more protective against weight gain than a prolonged negative energy balance from dietary restrictions.

This study tested whether energy balance or energy flux predict future weight gain, in a group of healthy-weight adolescents and slightly heavier young adults, by using objective method to estimate energy intake and expenditure.
- Energy balance = Total Energy Intake (TEI) - Total Energy Expenditure (TEE)
- Energy flux = TEI + TEE

It was found that Energy Balance did NOT predict weight gain, but Low Energy Flux predicted future body fat gain (moderate relationship). What is even more surprising is that, the low energy flux group that showed increases in body fat was in a negative energy balance at baseline, whereas the high energy flux group that showed decreases in body fat was in a positive energy balance at baseline.

The results are consistent with the thesis that homeostatic regulation of body weight is more effective when energy balance is sustained at high levels of energy intake and energy expenditure, supporting the premise that energy-restrictive diets, particularly when coupled with low exercise, may not be optimal for weight loss.

This implies that regular physical activity may be key for effective long-term weight management, extending previous evidence that exercise is the best predictor of successful weight loss maintenance. Low-calorie diets theoretically reduce volitional physical activity and nonexercise-associated thermogenesis, which promote weight regain because they foster energy conservation.

What can we improve in our weight management strategy based on this (objective) finding?

Hume, Yokum, and Stice. Am J Clin Nutr 2016. doi: 10.3945/ajcn.115.127753.