March 10, 2019

Fasting

The mouse trap: lost in translation?

“The great majority of how we understand disease, and attempt to cure it,” writes Engber, “derives from a couple of rodents.” About 4/5ths of all animal studies reported in biomedical research papers from 1950-2010 were done in rodents (59% in mice, 18% in rats).

Read Time 2 minutes

This article* is an oldie and a goodie: The Mouse Trap by Daniel Engber. The author provides the historical context for how and why we arrived at what amounts to a monoculture in medical research. “The great majority of how we understand disease, and attempt to cure it,” writes Engber, “derives from a couple of rodents.” About 4/5ths of all animal studies reported in biomedical research papers from 1950-2010 were done in rodents (59% in mice, 18% in rats).

* This is a three-part series and the link above provides all three parts in one in a text-only version. Here’s Part I, Part II, and Part III with all of the accompanying images and videos.

It seems most of us are numb to the caveat that’s included (or should be included) in rodent research: ‘this finding may not translate to humans.’ But we shouldn’t be. For example, one study found that fewer than 10% of highly promising basic science discoveries enter routine clinical use within 20 years, “supporting the notion that basic science research rarely translates into clinical research and clinical practice, even when they seem highly promising,” writes John Ioannidis and his colleagues in 2003.

Perhaps a related story from 2012: the New York Times reported on a study in mice showing autophagy is accelerated by exercise, and this may be a crucial benefit of physical activity. Autophagy reportedly increased in cardiac and skeletal muscle after 30 minutes of treadmill running and reached a plateau at 80 minutes.

This sounds great…for mice. Remember the caveat? The basal metabolic rate (per gram of bodyweight) of a mouse is roughly seven times faster than a human’s. Studies have also shown that if you fast a mouse for two days it loses 20% of its body weight. (To put this in perspective, this is the equivalent of starting a fast on Sunday night weighing 180 lbs. and dropping 36 lbs. by Tuesday.) Humans live roughly 40 times longer than mice. Think about how this might impact translation from mouse to human.

Mice fasted for 18 hours lose about 15% of their body weight. Keep this in mind if someone is telling you that intermittent fasting and exercise boosts autophagy. It might. (And boy are “intermittent fasting” and “exercise” umbrella terms.) They may be unknowingly relying on research in rodents. If autophagy is upregulated in response to nutrient deprivation — and the extent and duration of the deprivation matters — it doesn’t seem unreasonable to think that we’re talking about two entirely different situations when comparing mice to humans, whether comparing the effects of a 30 minute run on the treadmill or skipping breakfast.

Unfortunately, it’s very difficult to study autophagy in humans (and mice are not furry little humans). Have I mentioned how nice it would be if we could?

– Peter

Disclaimer: This blog is for general informational purposes only and does not constitute the practice of medicine, nursing or other professional health care services, including the giving of medical advice, and no doctor/patient relationship is formed. The use of information on this blog or materials linked from this blog is at the user's own risk. The content of this blog is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Users should not disregard, or delay in obtaining, medical advice for any medical condition they may have, and should seek the assistance of their health care professionals for any such conditions.
[gravityform id="5" title="false" description="false"]
<div class='gf_browser_unknown gform_wrapper form--inline_wrapper gtm--newsletter-form-popup_wrapper gform_legacy_markup_wrapper' id='gform_wrapper_5' ><form method='post' enctype='multipart/form-data' id='gform_5' class='form--inline gtm--newsletter-form-popup gform_legacy_markup' action='/the-mouse-trap-lost-in-translation/' novalidate> <div class='gform_body gform-body'><ul id='gform_fields_5' class='gform_fields top_label form_sublabel_below description_below'><li id="field_5_1" class="gfield gfield_contains_required field_sublabel_below field_description_below gfield_visibility_visible" data-js-reload="field_5_1"><label class='gfield_label' for='input_5_1' >Email<span class="gfield_required"><span class="gfield_required gfield_required_asterisk">*</span></span></label><div class='ginput_container ginput_container_email'> <input name='input_1' id='input_5_1' type='email' value='' class='large' placeholder='Your email address' aria-required="true" aria-invalid="false" /> </div></li><li id="field_5_10" class="gfield gfield--width-full field_sublabel_below field_description_below gfield_visibility_visible" data-js-reload="field_5_10"><label class='gfield_label' for='input_5_10' >CAPTCHA</label><div id='input_5_10' class='ginput_container ginput_recaptcha' data-sitekey='6LeuYQ0dAAAAAHQqB_Z3xNQAwCRlN5ykarrLsrZw' data-theme='light' data-tabindex='-1' data-size='invisible' data-badge='bottomright'></div></li><li id="field_5_2" class="gfield gform_hidden field_sublabel_below field_description_below gfield_visibility_visible" data-js-reload="field_5_2"><div class='ginput_container ginput_container_text'><input name='input_2' id='input_5_2' type='hidden' class='gform_hidden' aria-invalid="false" value='The mouse trap: lost in translation?' /></div></li><li id="field_5_3" class="gfield gform_hidden field_sublabel_below field_description_below gfield_visibility_visible" data-js-reload="field_5_3"><div class='ginput_container ginput_container_text'><input name='input_3' id='input_5_3' type='hidden' class='gform_hidden' aria-invalid="false" value='https://peterattiamd.com/the-mouse-trap-lost-in-translation/' /></div></li><li id="field_5_4" class="gfield gform_hidden field_sublabel_below field_description_below gfield_visibility_visible" data-js-reload="field_5_4"><div class='ginput_container ginput_container_text'><input name='input_4' id='input_5_4' type='hidden' class='gform_hidden' aria-invalid="false" value='' /></div></li><li id="field_5_5" class="gfield gform_hidden field_sublabel_below field_description_below gfield_visibility_visible" data-js-reload="field_5_5"><div class='ginput_container ginput_container_text'><input name='input_5' id='input_5_5' type='hidden' class='gform_hidden' aria-invalid="false" value='' /></div></li><li id="field_5_9" class="gfield gform_hidden field_sublabel_below field_description_below gfield_visibility_visible" data-js-reload="field_5_9"><div class='ginput_container ginput_container_text'><input name='input_9' id='input_5_9' type='hidden' class='gform_hidden' aria-invalid="false" value='' /></div></li><li id="field_5_8" class="gfield gform_hidden field_sublabel_below field_description_below gfield_visibility_visible" data-js-reload="field_5_8"><div class='ginput_container ginput_container_text'><input name='input_8' id='input_5_8' type='hidden' class='gform_hidden' aria-invalid="false" value='' /></div></li><li id="field_5_7" class="gfield gform_hidden field_sublabel_below field_description_below gfield_visibility_visible" data-js-reload="field_5_7"><div class='ginput_container ginput_container_text'><input name='input_7' id='input_5_7' type='hidden' class='gform_hidden' aria-invalid="false" value='' /></div></li><li id="field_5_6" class="gfield gform_hidden field_sublabel_below field_description_below gfield_visibility_visible" data-js-reload="field_5_6"><div class='ginput_container ginput_container_text'><input name='input_6' id='input_5_6' type='hidden' class='gform_hidden' aria-invalid="false" value='' /></div></li></ul></div> <div class='gform_footer top_label'> <input type='submit' id='gform_submit_button_5' class='gform_button button' value='Sign up' onclick='if(window["gf_submitting_5"]){return false;} if( !jQuery("#gform_5")[0].checkValidity || jQuery("#gform_5")[0].checkValidity()){window["gf_submitting_5"]=true;} ' onkeypress='if( event.keyCode == 13 ){ if(window["gf_submitting_5"]){return false;} if( !jQuery("#gform_5")[0].checkValidity || jQuery("#gform_5")[0].checkValidity()){window["gf_submitting_5"]=true;} jQuery("#gform_5").trigger("submit",[true]); }' /> <input type='hidden' class='gform_hidden' name='is_submit_5' value='1' /> <input type='hidden' class='gform_hidden' name='gform_submit' value='5' /> <input type='hidden' class='gform_hidden' name='gform_unique_id' value='' /> <input type='hidden' class='gform_hidden' name='state_5' value='WyJbXSIsIjU1MGM3MDVmNDUwOTYxNmQyYTU0NTkwMjUzZjU2NGI1Il0=' /> <input type='hidden' class='gform_hidden' name='gform_target_page_number_5' id='gform_target_page_number_5' value='0' /> <input type='hidden' class='gform_hidden' name='gform_source_page_number_5' id='gform_source_page_number_5' value='1' /> <input type='hidden' name='gform_field_values' value='' /> </div> <p style="display: none !important;"><label>&#916;<textarea name="ak_hp_textarea" cols="45" rows="8" maxlength="100"></textarea></label><input type="hidden" id="ak_js_3" name="ak_js" value="170"/><script>document.getElementById( "ak_js_3" ).setAttribute( "value", ( new Date() ).getTime() );</script></p></form> </div>
[gravityform id="1" title="false" description="false"]
<div class='gf_browser_unknown gform_wrapper form--inline_wrapper gtm--newsletter-form_wrapper gform_legacy_markup_wrapper' id='gform_wrapper_1' ><form method='post' enctype='multipart/form-data' id='gform_1' class='form--inline gtm--newsletter-form gform_legacy_markup' action='/the-mouse-trap-lost-in-translation/' novalidate> <div class='gform_body gform-body'><ul id='gform_fields_1' class='gform_fields top_label form_sublabel_below description_below'><li id="field_1_1" class="gfield gfield_contains_required field_sublabel_below field_description_below gfield_visibility_visible" data-js-reload="field_1_1"><label class='gfield_label' for='input_1_1' >Email<span class="gfield_required"><span class="gfield_required gfield_required_asterisk">*</span></span></label><div class='ginput_container ginput_container_email'> <input name='input_1' id='input_1_1' type='email' value='' class='large' placeholder='Your email address' aria-required="true" aria-invalid="false" /> </div></li><li id="field_1_11" class="gfield gfield--width-full ohnohoney field_sublabel_below field_description_below gfield_visibility_hidden" data-js-reload="field_1_11"><div class='admin-hidden-markup'><i class='gform-icon gform-icon--hidden'></i><span>Hidden</span></div><label class='gfield_label' for='input_1_11' >H-o-n-e-y-p-o-t</label><div class='ginput_container ginput_container_text'><input name='input_11' id='input_1_11' type='text' value='' class='large' aria-invalid="false" /> </div></li><li id="field_1_10" class="gfield gfield--width-full field_sublabel_below field_description_below gfield_visibility_visible" data-js-reload="field_1_10"><label class='gfield_label' for='input_1_10' >CAPTCHA</label><div id='input_1_10' class='ginput_container ginput_recaptcha' data-sitekey='6LeuYQ0dAAAAAHQqB_Z3xNQAwCRlN5ykarrLsrZw' data-theme='dark' data-tabindex='-1' data-size='invisible' data-badge='bottomleft'></div></li><li id="field_1_2" class="gfield gform_hidden field_sublabel_below field_description_below gfield_visibility_visible" data-js-reload="field_1_2"><div class='ginput_container ginput_container_text'><input name='input_2' id='input_1_2' type='hidden' class='gform_hidden' aria-invalid="false" value='The mouse trap: lost in translation?' /></div></li><li id="field_1_3" class="gfield gform_hidden field_sublabel_below field_description_below gfield_visibility_visible" data-js-reload="field_1_3"><div class='ginput_container ginput_container_text'><input name='input_3' id='input_1_3' type='hidden' class='gform_hidden' aria-invalid="false" value='https://peterattiamd.com/the-mouse-trap-lost-in-translation/' /></div></li><li id="field_1_4" class="gfield gform_hidden field_sublabel_below field_description_below gfield_visibility_visible" data-js-reload="field_1_4"><div class='ginput_container ginput_container_text'><input name='input_4' id='input_1_4' type='hidden' class='gform_hidden' aria-invalid="false" value='' /></div></li><li id="field_1_5" class="gfield gform_hidden field_sublabel_below field_description_below gfield_visibility_visible" data-js-reload="field_1_5"><div class='ginput_container ginput_container_text'><input name='input_5' id='input_1_5' type='hidden' class='gform_hidden' aria-invalid="false" value='' /></div></li><li id="field_1_9" class="gfield gform_hidden field_sublabel_below field_description_below gfield_visibility_visible" data-js-reload="field_1_9"><div class='ginput_container ginput_container_text'><input name='input_9' id='input_1_9' type='hidden' class='gform_hidden' aria-invalid="false" value='' /></div></li><li id="field_1_8" class="gfield gform_hidden field_sublabel_below field_description_below gfield_visibility_visible" data-js-reload="field_1_8"><div class='ginput_container ginput_container_text'><input name='input_8' id='input_1_8' type='hidden' class='gform_hidden' aria-invalid="false" value='' /></div></li><li id="field_1_7" class="gfield gform_hidden field_sublabel_below field_description_below gfield_visibility_visible" data-js-reload="field_1_7"><div class='ginput_container ginput_container_text'><input name='input_7' id='input_1_7' type='hidden' class='gform_hidden' aria-invalid="false" value='' /></div></li><li id="field_1_6" class="gfield gform_hidden field_sublabel_below field_description_below gfield_visibility_visible" data-js-reload="field_1_6"><div class='ginput_container ginput_container_text'><input name='input_6' id='input_1_6' type='hidden' class='gform_hidden' aria-invalid="false" value='' /></div></li><li id="field_1_12" class="gfield gform_validation_container field_sublabel_below field_description_below gfield_visibility_visible" data-js-reload="field_1_12"><label class='gfield_label' for='input_1_12' >Comments</label><div class='ginput_container'><input name='input_12' id='input_1_12' type='text' value='' autocomplete='new-password'/></div><div class='gfield_description' id='gfield_description_1_12'>This field is for validation purposes and should be left unchanged.</div></li></ul></div> <div class='gform_footer top_label'> <input type='submit' id='gform_submit_button_1' class='gform_button button' value='Sign up' onclick='if(window["gf_submitting_1"]){return false;} if( !jQuery("#gform_1")[0].checkValidity || jQuery("#gform_1")[0].checkValidity()){window["gf_submitting_1"]=true;} ' onkeypress='if( event.keyCode == 13 ){ if(window["gf_submitting_1"]){return false;} if( !jQuery("#gform_1")[0].checkValidity || jQuery("#gform_1")[0].checkValidity()){window["gf_submitting_1"]=true;} jQuery("#gform_1").trigger("submit",[true]); }' /> <input type='hidden' class='gform_hidden' name='is_submit_1' value='1' /> <input type='hidden' class='gform_hidden' name='gform_submit' value='1' /> <input type='hidden' class='gform_hidden' name='gform_unique_id' value='' /> <input type='hidden' class='gform_hidden' name='state_1' value='WyJbXSIsIjU1MGM3MDVmNDUwOTYxNmQyYTU0NTkwMjUzZjU2NGI1Il0=' /> <input type='hidden' class='gform_hidden' name='gform_target_page_number_1' id='gform_target_page_number_1' value='0' /> <input type='hidden' class='gform_hidden' name='gform_source_page_number_1' id='gform_source_page_number_1' value='1' /> <input type='hidden' name='gform_field_values' value='' /> </div> <p style="display: none !important;"><label>&#916;<textarea name="ak_hp_textarea" cols="45" rows="8" maxlength="100"></textarea></label><input type="hidden" id="ak_js_4" name="ak_js" value="213"/><script>document.getElementById( "ak_js_4" ).setAttribute( "value", ( new Date() ).getTime() );</script></p></form> </div>
Facebook icon Twitter icon Instagram icon Pinterest icon Google+ icon YouTube icon LinkedIn icon Contact icon